Research Article

Tumor Biology

, Volume 33, Issue 1, pp 121-129

CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function

  • Jahyang ChoiAffiliated withCancer Research Institute, Seoul National University College of Medicine and HospitalInnovative Research Institute for Cell Therapy, Seoul National University College of Medicine and Hospital
  • , Beomseok SuhAffiliated withCancer Research Institute, Seoul National University College of Medicine and Hospital
  • , Yong-Oon AhnAffiliated withCancer Research Institute, Seoul National University College of Medicine and HospitalInnovative Research Institute for Cell Therapy, Seoul National University College of Medicine and Hospital
  • , Tae Min KimAffiliated withCancer Research Institute, Seoul National University College of Medicine and HospitalInnovative Research Institute for Cell Therapy, Seoul National University College of Medicine and HospitalDepartment of Internal Medicine, Seoul National University College of Medicine and Hospital
  • , Jeong-Ok LeeAffiliated withCancer Research Institute, Seoul National University College of Medicine and HospitalDepartment of Internal Medicine, Seoul National University College of Medicine and Hospital
  • , Se-Hoon LeeAffiliated withCancer Research Institute, Seoul National University College of Medicine and HospitalInnovative Research Institute for Cell Therapy, Seoul National University College of Medicine and HospitalDepartment of Internal Medicine, Seoul National University College of Medicine and Hospital
  • , Dae Seog HeoAffiliated withCancer Research Institute, Seoul National University College of Medicine and HospitalInnovative Research Institute for Cell Therapy, Seoul National University College of Medicine and HospitalDepartment of Internal Medicine, Seoul National University College of Medicine and Hospital Email author 

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Abstract

Myeloid-derived suppressor cells (MDSCs) are a subpopulation of myeloid cells with immunosuppressive function whose numbers are increased in conditions such as chronic infection, trauma, and cancer. Unlike murine MDSCs defined as CD11b+/Gr-1+, there are no specific markers for human MDSCs. The goal of this study was to delineate a specific human MDSCs subpopulation in granulocytes from terminal cancer patients and investigate its clinical implications. Here, we show that the CD15+/CD16low subset was increased in terminal cancer patients compared with healthy donors (P = 0.009). Phorbol 12-myristate 13-acetate-activated granulocytes (CD16low/CD66b++/CD15+) that have a phenotype similar to MDSCs from cancer patients, effectively suppressed both proliferation and cytotoxicity of normal T cells. Among cancer patients, T-cell proliferation was highly suppressed by granulocytes isolated from terminal cancer patients with a high proportion of CD15+/CD16low cells. Patients with low peripheral blood levels of CD15+/CD16low cells had significantly longer survival than those with high levels (P = 0.0011). Patients with higher levels of CD15+/CD16low also tended to have poor performance status (P = 0.05). These data suggest that CD15+/CD16low granulocytes found in terminal cancer patients may play a role in the progression of cancer by inhibiting tumor immunity.

Keywords

MDSCs CD15+/CD16low granulocytes T-cell suppression Tumor immunity Immune monitoring